Herpes simplex virus type 2 is a common sexually transmitted disease with an estimated incidence of 500,000 new cases/year. The recurrent genital lesions are physically debilitating and cause intolerable mental and social anguish. Secondary complications include elevated abortion rates, increases in the incidence of fetal malformations, and severe herpetic infections of newborn infants. Public interest supports the development of preventive therapy for HSV-2 infections. However, effective means for the prevention/cure of herpetic recurrences cannot be developed until we achieve a basic understanding of the role played by virus specific immunity in primary and recurrent cutaneous disease, ganglionic latency and reinfection. Our goal is to develop a better understanding of the immunobiology of HSV infections, including the identification of viral proteins that play key regulatory functions in cutaneous infection/reinfection, recurrent disease and ganglionic latency. Vaccinia recombinants containing the HSV glycoprotein genes gD, gB, gC, their achorless versions (glycoprotein lacks the transmembrane anchor) and multiple combinations of these 3 genes will be studied. The expression of these genes in various cell species will be determined by immunoprecipitation of cell extracts labeled with 35S-methionine, 3H-glucosamine or 3H-mannose and immunoflourescent staining of live cells with panels of monoclonal antibodies that recognize different antigenic domains on the appropriate glycoproteins. The recombinants will be studied for their ability to protect from primary and recurrent HSV-2 or HSV-1 cutaneous disease, ganglionic infection and fatal challenge. The findings will be corelated with the ability of the recombinants to induce HSV specific immunity including: (i) varus specific antibody (neutralizing, cytolytic, mediating cellular cytotoxicity) and lymphoproliferation, (ii) fine specificity of HSV specific immunoglobulins, (iii) adoptive protection against HSV challenge and phenotype of transferred cells and (iv) virus-specific cytotoxic T lymphocytes (Tc): regulatory (suppressor) functions.